Mechanisms underlying the increased cardiac norepinephrine spillover in heart failure

Ramchandra, Rohit, Hood, Sally G., Xing, Daniel, Lambert, Gavin W., and May, Clive N. (2018) Mechanisms underlying the increased cardiac norepinephrine spillover in heart failure. American Journal of Physiology-Heart and Circulatory Physiology, 315 (2). H340-H347.

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Abstract

Patients with heart failure (HF) have increased levels of cardiac norepinephrine (NE) spillover, which is an independent predictor of mortality. We hypothesized that this increase in NE spillover in HF depends not only on increases in sympathetic nerve activity (SNA) but also on changes in the mechanisms controlling NE release and reuptake. Such changes would lead to differences between the increases in directly recorded SNA and NE spillover to the heart in HF. Experiments were conducted in conscious sheep implanted with electrodes to record cardiac SNA (CSNA). In addition, arterial pressure and cardiac NE spillover were determined. In HF, the levels of both CSNA (102 ± 8 vs. 45 ± 8 bursts/min, P < 0.05) and cardiac NE spillover (21.6 ± 3.8 vs. 3.9 ± 0.8 pmol/min, P < 0.05) were significantly higher than in normal control animals. In HF, baroreflex control of cardiac NE spillover was impaired, and when CSNA was abolished by increasing arterial pressure, there was no reduction in cardiac NE spillover. A decrease in cardiac filling pressures in the HF group led to a significant increase in CSNA, but it significantly decreased cardiac NE spillover. In HF, the levels of cardiac NE spillover were enhanced above those expected from the high level of SNA, suggesting that changes in mechanisms controlling NE release and reuptake further increase the high level of NE at the heart, which will act to enhance the deleterious effects of increased CSNA in HF.

Item ID: 82161
Item Type: Article (Research - C1)
ISSN: 1522-1539
Keywords: heart failure; sympathetic nerve activity; norepinephrine spillover
Copyright Information: © 2018 the American Physiological Society
Date Deposited: 26 Mar 2024 04:47
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 100%
42 HEALTH SCIENCES > 4299 Other health sciences > 429999 Other health sciences not elsewhere classified @ 0%
SEO Codes: 20 HEALTH > 2099 Other health > 209999 Other health not elsewhere classified @ 100%
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